Project Summary It is clear that the gut microbiome significantly influences human health, but key knowledge gaps remain in our understanding of microbial function during various disease states. Microorganisms have evolved a great diversity of enzymes and metabolisms to biochemically transform environmental toxins, and are biochemically active against at least some toxic xenobiotic compounds. However, how these activities influence human health, positively or negatively, are poorly understood. Human exposure to potential insults, ranging from chemotherapeutics (sometimes referred to as xenobiotics) to the ingestion of food and/or water contaminated with toxic metal(loid)s, can result in a variety of pathologic sequelae depending on the dose and timing of exposure. For example, arsenic has been rated by the U.S.E.P.A. as the number one environmental toxin based on both its abundance in the environment and risk to human health. Presumably, microbes in the gut are among the first cells to receive and transform harmful chemicals, whatever the source, but outcomes and consequences of this exposure are largely unknown. Is microbiome biochemistry relating to toxins and/or synthetic xenobiotic compounds beneficial to human cells? Primary goals for both basic and clinical researchers are to: 1) identify important toxin biochemistry in the gut, 2) mitigate detrimental toxin biotransformations by microbes, and 3) promote beneficial microbiome toxin biochemistry so as to better treat diseases that arise from environmental exposures.